Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells
The complexity of the process of metastasis is widely recognized. We report herein on a recurrent feature of high compared to low metastatic cells that is linked to their ability to survive early after their arrival at secondary sites. Using novel fluorescent-based imaging strategies that assess tum...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-03-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558612800376 |
| _version_ | 1818068344790581248 |
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| author | Sung-Hyeok Hong Ling Ren Arnulfo Mendoza Ananth Eleswarapu Chand Khanna |
| author_facet | Sung-Hyeok Hong Ling Ren Arnulfo Mendoza Ananth Eleswarapu Chand Khanna |
| author_sort | Sung-Hyeok Hong |
| collection | DOAJ |
| description | The complexity of the process of metastasis is widely recognized. We report herein on a recurrent feature of high compared to low metastatic cells that is linked to their ability to survive early after their arrival at secondary sites. Using novel fluorescent-based imaging strategies that assess tumor cell interaction with the lung microenvironment, we have determined that most high and low metastatic cells can be distinguished within 6 hours of their arrival in the lung and further that this difference is defined by the ability of high metastatic cells to resist apoptosis at the secondary site. Despite the complexity of the metastatic cascade, the performance of cells during this critical window is highly defining of their metastatic proclivity. To explore mechanisms, we next evaluated biochemical pathways that may be linked to this survival phenotype in highly metastatic cells. Interestingly, we found no association between the Akt survival pathway and this metastatic phenotype. Of all pathways examined, only protein kinase C (PKC) activation was significantly linked to survival of highly metastatic cells. These data provide a conceptual understanding of a defining difference between high and low metastatic cells. The connection to PKC activation may provide a biologic rationale for the use of PKC inhibition in the prevention of metastatic progression. |
| first_indexed | 2024-12-10T15:38:05Z |
| format | Article |
| id | doaj.art-b6a579e25098486fb1ad78c7c13a6a56 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-10T15:38:05Z |
| publishDate | 2012-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-b6a579e25098486fb1ad78c7c13a6a562022-12-22T01:43:11ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022012-03-0114324925810.1593/neo.111498Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic CellsSung-Hyeok Hong0Ling Ren1Arnulfo Mendoza2Ananth Eleswarapu3Chand Khanna4Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USATumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USATumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USATumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USATumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAThe complexity of the process of metastasis is widely recognized. We report herein on a recurrent feature of high compared to low metastatic cells that is linked to their ability to survive early after their arrival at secondary sites. Using novel fluorescent-based imaging strategies that assess tumor cell interaction with the lung microenvironment, we have determined that most high and low metastatic cells can be distinguished within 6 hours of their arrival in the lung and further that this difference is defined by the ability of high metastatic cells to resist apoptosis at the secondary site. Despite the complexity of the metastatic cascade, the performance of cells during this critical window is highly defining of their metastatic proclivity. To explore mechanisms, we next evaluated biochemical pathways that may be linked to this survival phenotype in highly metastatic cells. Interestingly, we found no association between the Akt survival pathway and this metastatic phenotype. Of all pathways examined, only protein kinase C (PKC) activation was significantly linked to survival of highly metastatic cells. These data provide a conceptual understanding of a defining difference between high and low metastatic cells. The connection to PKC activation may provide a biologic rationale for the use of PKC inhibition in the prevention of metastatic progression.http://www.sciencedirect.com/science/article/pii/S1476558612800376 |
| spellingShingle | Sung-Hyeok Hong Ling Ren Arnulfo Mendoza Ananth Eleswarapu Chand Khanna Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells Neoplasia: An International Journal for Oncology Research |
| title | Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells |
| title_full | Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells |
| title_fullStr | Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells |
| title_full_unstemmed | Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells |
| title_short | Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells |
| title_sort | apoptosis resistance and pkc signaling distinguishing features of high and low metastatic cells |
| url | http://www.sciencedirect.com/science/article/pii/S1476558612800376 |
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